Structural nucleic acid nanotechnology allows for production of two- and three-dimensional nanometer-scale structures based on nucleic acids (e.g., DNA). The structures are produced, for example, through predictable hybridization of DNA into its double-stranded form. In some instances, structures may be produced (referred to herein as “folded”) using a very long strand, termed a “scaffold” strand, and a number of short strands, referred to as either oligonucleotides or “staple” strands. Each staple strand binds the scaffold strand at two or more non-contiguous regions, resulting in various, typically predictable, shapes. Nucleic acid structures may also be produced using staple strands in the absence of a scaffold strand. Depending on the size of the resulting shape, different numbers of strands may be used, ranging from as few as three or four strands to many hundreds or even thousands of strands to produce a stable nucleic acid nano structure.
Nonetheless, in uncontrolled, undefined environments (e.g., in vivo), nucleic acid structures may be unstable as a result of their susceptibility to degradation through a number of different mechanisms, including but not limited to nuclease degradation, depletion of cations, and sensitivity to pH.